POS0548 EVALUATION OF PHYSICIAN GLOBAL ASSESSMENT IN PATIENTS WITH b/tsDMARD THERAPY SELECTION ALIGNED WITH A MOLECULAR SIGNATURE RESPONSE CLASSIFIER RESULTS: AN ANALYSIS FROM THE STUDY TO ACCELERATE INFORMATION OF MOLECULAR SIGNATURES (AIMS) IN RHEUMATOID ARTHRITIS
Authors: E. Connolly-Strong, L. Zhang, S. Asgarian
Journal: Annals of the Rheumatic Diseases (2022)

Background Despite drug therapies that improve lives, tens of millions of patients annually are prescribed therapy using a “trial and error” approach because, until recently, it was not possible to personalize treatment using a patient’s unique molecular profile. A blood-based molecular signature response classifier (MSRC) was shown to predict non-response to TNFi therapies in patients. MSRC integrates disease-associated RNA transcripts, and clinical features (anti-CCP, sex, BMI, PGA). [1] A recent study demonstrated that patient response to treatment informed by MSRC was more than 3 times better when MRSC informed therapy selection (predicted non-responders [alt-MOA] =34.8% vs predicted non-responders [TNFi] = 10.3%, p-value = 0.05). [1] Furthermore, when patients without a non-response signal from MSRC were prescribed a TNFi for treatment, their outcomes were improved by 5 times compared to the cohort receiving TNFi therapy despite a signal of non-response from MSRC (no prediction -[TNFi] = 45.8% vs predicted non-responder[TNFi]= 10.3%, p-value = 0.005) [1] Objectives The objective of the Study to Accelerate Information of Molecular Signatures (AIMS) in RA is to build a clinical/molecular database of longitudinal data from RA patients managed a real-world, settings with a focus on utilization of the MSRC test (PrismRA Scipher Medicine). Physician Global Assessment scores were measured and assessed as the objective of this analysis. Methods This analysis reports on data from patients enrolled in AIMS who initiated a new b/tsDMARD, or continued existing therapy, following MSRC testing (n = 560). Patients were ≥18 years of age with a clinical diagnosis of RA. The cohort was divided into patients whose targeted therapy selection was Aligned (predicted non-responder (PNR)- [altMOA], no prediction of non-response (NP)- [TNFi] or [altMOA] and Not Aligned (PNR- [TNFi]) with the MSRC test results. Improvement from baseline of MDGA was evaluated at 3 &amp; 6 ms and swollen joints at 3ms. Results Predicted non-responders prescribed an alt-MOA had significant improvement in MDGA scores at 3 &amp; 6 ms compared to predicted non-responders prescribed a TNFi (3m: PNR-[altMOA]- 18.4% (n=163) vs PRN-[TNFi] 7.2% (n=140), p-value – 0.010, 6m: PNR-[altMOA]- 13.1% (n=80) vs PRN-[TNFi] -1.11% (n=90), p-value – 0.013). Patients without the molecular signature prescribed a TNFi showed a trend of more improvement in MDGA scores at 3 &amp; 6ms compared to patients with the molecular signature prescribed a TNFi (3m: NP-[TNFi]- 11.5% (n=134) vs PRN-[TNFi] 7.2% (n=140), p-value – 0.791, 6m: NP-[TNFi]- 13.3% (n=76) vs PRN-[TNFi] -1.11% (n=90), p-value – 0.075) (Figure 1). Moreover, predicted non-responders prescribed an alt-MOA showed a trend of improvement in swollen joints at 3ms compared to predicted non-responders prescribed a TNFi (PNR-[altMOA]- 3.15% (n=163) vs PRN-[TNFi] 1.7% (n=140), p-value – 0.08). Patients without the molecular signature prescribed a TNFi showed significantly more improvement in swollen joints at 3ms (NP-[TNFi]- 3.71% (n=134) vs PRN-[TNFi] 1.7% (n=140), p-value – &lt;0.001). Characteristics of the cohort are reported in the Table 1. Table 1. Characteristic PNR-TNFin=159 PNR-altMOAn=176 NP-TNFin=145 NP-altMOAn=80 P-value (PNR-TNFi vs NP-TNFi) P-value (PNR-TNFi vs PNR-altMOA) Age,mean (SD) 53.5 (13.8) 57.6 (12.9) 55.9 (14.4) 59.7 (13.2) 0.135 0.005 Race, n (%) 0.346 0.896 White 128 (81) 142 (81) 124 (86) 64 (80) Black 11 (7) 11 (6) 9 (6) 5 (6) Other 20(13) 23(13) 12(8) 11 (14) CDAI at baseline (SD) 34.1 (15.8) 38.5 (16.3) 28.5 (15) 26.5 (15.6) 0.002 0.012 TNFi Navie at baseline, n (%) 128 (81) 148 (84) 120 (83) 71 (89) 0.672 0.473 Figure 1. Conclusion The incorporation of MSCR testing into the b/tsDMARD selection process can improve patient outcomes and can help identify which patient may be more or less responsive TNFi therapies. References [1]Strand, V., et al.Expert Rev Mol Diagn, 2021 Disclosure of Interests Erin Connolly-Strong Shareholder of: Scipher, Lixia Zhang Shareholder of: Scipher, Sam Asgarian Shareholder of: Scipher.